The principal subjects of this project are the mechanisms that underlie membrane assembly and the conditions that affect the stability of cell membranes. We have demonstrated that cell membrane lipids exist in a critical state at physiological temperatures, and that the physicochemical properties exhibited by the critical state are unique and are not present at any other temperature. The principal determinants for membrane assembly and the stability of the membranes are the physiological temperature and the lipid composition. To examine the significance of the critical state to membrane asembly in the absence of lipid biosynthesis we have studied the nascent membranes in L. pictus embryos incubated at temperatures of 10-23 degrees C; until the blastula stage of embryogenesis is completed no de novo biosysnthesis of lipid is observed. Yet the lipid composition of the nascent membranes varies with the incubation temperature. This signifies that membranes assemble with the lipids that are selected by a temperature dependent process from a static pool of yolk lipids. Comparison of the lipid states which form in vivo and in vitro at each incubation temperature indicates they are identical. Thus, we assume that the lipid portion of the nascent membrane forms by a self-assembly process that is driven by the requirements of the critical bilayer state. The second aspect of this project: the stability of cell membranes has been examined within the context of disease-related lipid defects. In the presence of a membrane lipid defect the critical state, normally the most stable structure at physiological temperatures, spontaneously forms another, nonviable, lipid structure. Some of these structures have been identified; the morphology, governed by the equilibrium phase diagram of the lipid, is typically multilamellar. In Alzheimer's disease a deficit in plasmalogen phosphatidylethanolamine correlates with a change in the critical state that has now been reproduced in vitro, by simulating the composition of the diseased state.